Objective: To investigate and analyze the effect of He-Ne laser, recombinant human interferon α-2b ointment and gabapentin on skin lesion healing, sleep, pain and disease course in acute herpes zoster ophthalmicus. Methods: Sixty patients with acute herpes zoster ophthalmicus were collected from January 2017 to January 2020 in our hospital. According to the different treatment, they were divided into an experimental group (32 cases) and a control group (28 cases). The patients in the control group received routine basic treatment including antiviral, neurotrophic therapy, interferon α-2b ointment and gabapentin, and the experimental group was treated with He-Ne laser on the basis of control group treatment. The time of detumescence, blister stopping, scab formation, scab removal and pain relief, Visual Analogue Scale (VAS) score, sleep time, adverse reactions, and postherpetic neuralgia were collected and analyzed. Results: Before treatment, there was no significant difference in the observation indexes between the two groups (P>0.05); after treatment, the observation indexes of skin rash (detumescence, blister stopping, scab formation, scab removal) and pain relief time in the experimental group were significantly less than those in the control group, and the scab removal rate on the 4th and 7th days post-treatment in the experimental group was significantly higher than that in the control group; after treatment, the sleep duration was prolonged, and the VAS score was decreased. For pain relief and prolonging sleep time, the experimental group was better than the control group, and the difference was statistically significant P<0.05).There was no significant difference in scab removal rate on 2, 14 and 28 days post-treatment (P>0.05). The effective rate in the experimental group (93.75%) was significantly higher than that in the control group (75%), and the difference was statistically significant (P=0.047); there was no significant difference in PHN and adverse reactions between the two groups (P>0.05). Conclusion: He-Ne laser combined with interferon α-2b ointment and gabapentin is safe and effective in the treatment of acute herpes zoster ophthalmicus. It can significantly relieve the acute pain, promote the recovery of rash, improve sleep quality, shorten the disease course, and can be actively promoted in clinical usage.